Thursday, May 6, 2010

For the first time, researchers -- all Cornell scientists -- have characterized the structure of a protein that belongs to certain enzymes that are essential for proper functioning in all life forms, from yeast to humans.

The enzymes, belonging to the so-called Sac family, are involved in cellular signaling and membrane trafficking. Scientists have found that when the gene that expresses Sac enzymes is deleted in animals, the animals die, and mutations of related genes in humans lead to cancers and such neurodegenerative hereditary diseases as Charcot-Marie-Tooth Type 4J (CMT4J) and Lou Gehrig's disease.

Researchers from Cornell's Weill Institute of Cell and Molecular Biology, reporting online in the Journal of the European Molecular Biology Organization, have characterized for the first time the crystal structure of the Sac1 protein in yeast. Yeast serves as a model organism for all cells; most of the 6,000 genes in yeast are also found in humans. The Sac1 protein in yeast is a progenitor for related Sac proteins also found in plants and animals.

Understanding the Sac1 protein's structure opens the way for experiments that may reveal how these fundamental enzymes interact with cell membranes to enable essential cellular processes, which could also lead to drugs that target related diseases.

"This enzyme was first discovered in 1989, but no one had seen the atomic structure of this protein," said Yuxin Mao, an assistant professor of molecular biology and genetics and the paper's senior author. Andrew Manford, a graduate student in the lab of Scott Emr, director of the Weill Institute, is the paper's lead author. "Others have tried, but this is the first time" the protein's structure has been revealed, said Mao.

Much like an on and off switch, pathways that signal cells to divide, migrate or transport materials in and out of the cell are often activated by attaching a phosphate group to proteins or lipids (a process called phosphorylation) and similarly deactivated by the removal of the phosphate group. A class of enzymes called phosphatases mediates the removal of phosphates, and the Sac family of enzymes the Cornell researchers studied are lipid phosphatases. Such diseases as CMT4J and Lou Gehrig's disease occur when Sac family phosphatases fail to function properly, leading to a buildup of a group of phosphorylated lipids.

Mao and colleagues determined the structure by growing Sac protein crystals, which allowed researchers to view a protein's atomic structure through X-ray diffraction. Mao's lab used Cornell's synchrotron to solve the crystal structure of the Sac1 protein at an atomic resolution of less than 2 angstroms (two ten-millionths of a millimeter).

"This opens up biochemical studies of how these enzymes function -- it's a breakthrough in this direction of study," said Mao. "And it helps our studies of other members of the Sac family."

Researchers at McGill University are unlocking the mysteries of the little-known habits of dinosaurs in discovering that the entire western interior of North America was likely once populated by a single community of dinosaurs. According to a statistical analysis of the fossil record, dinosaurs were adept at coping with all sorts of environments, and not as restricted in their geographic ranges as previously thought.

The discovery was made by McGill Professor Hans Larsson and Matthew Vavrek, a PhD student at the University. Using data from the Paleobiology Database (http://www.paleodb.org/), they found that the difference in species between regions over North America was relatively low - low enough to consider it a single homogeneous fauna. The finding is significant as it confirms that dinosaur ecosystems may have been as large as continents. The paper is published in the April 19 issue of the journal Proceedings of the National Academy of Sciences.

The McGill team zeroed in on alpha diversity, the number of species in an immediate area, versus beta diversity, which are the differences in species between two different areas. Their research shows low beta biodiversity among these dinosaurs with values comparable to species living in homogeneous climates today, but on smaller geographic scales. "This is significant because we lack living analogues of a complete terrestrial megafauna living in those kinds of stable climates. The findings give us an insight into what kind of ranges these types of communities may have had," Larsson, a Canada Research Chair in Macroevolution, explained. "We also demonstrate that after more than a century of collecting dinosaurs in North America, we should expect to find about 16 types, on average, in any one region of western North America just before their mass extinction."

The long extinct dinosaurs are not just long dead fossils, but they offer a unique insight into a complex megafauna that responded to their environment. But even though they are extinct, they can tell us about the ecology of the animals we see today. "Despite their appearance, dinosaurs are ecologically very similar to mammals of today," Vavrek said. "They were able to colonize and dominate the landscape over very large distances, and were not nearly as constrained as we might have once thought."

By examining a single time slice, the Maastrichtian stage (71-65 million years ago) and all known specimens of dinosaurs from the Western Interior region of North America, the duo concluded that multiple dinosaur faunal regions did not exist. "Our results show low beta diversity and support a single dinosaur community within the entire Western Interior region. This widespread ecosystem was likely due to the homogenous climate present in this region at the time." said Larsson. "What is exciting about this result is that now we can begin to ask many more questions about how such a large homogeneous community of dinosaurs lived. Did they migrate, or have adequate amounts of gene flow between regional populations, or a mixture of both? How did this widespread dinosaur megafaunal community affect other animals and plants on the regional and continental scale? We're just beginning to scratch the surface of dinosaur ecology."

A University at Buffalo volcanologist, an expert in volcanic ash cloud transport, published a paper recently showing how the jet stream – the area in the atmosphere that pilots prefer to fly in – also seems to be the area most likely to be impacted by plumes from volcanic ash.

"That's a problem," says Marcus I. Bursik, PhD, one of the foremost experts on volcanic plumes and their effect on aviation safety, "because modern transcontinental and transoceanic air routes are configured to take advantage of the jet stream's power, saving both time and fuel.

"The interaction of the jet stream and the plume is likely a factor here," says Bursik, professor of geology in the UB College of Arts and Sciences. "Basically, planes have to fly around the plume or just stop flying, as they have, as the result of this eruption in Iceland."

In some cases, if the plume can be tracked well enough with satellites, pilots can steer around the plume, he notes, but that didn't work in this case because the ash drifted right over Britain.

Bursik participated in the first meetings in the early 1990s between volcanologists and the aviation industry to develop methods to ensure safe air travel in the event of volcanic eruptions. He and colleagues authored a 2009 paper called "Volcanic plumes and wind: Jet stream interaction examples and implications for air traffic" in the Journal of Volcanology and Geothermal Research.

"In the research we did, we found that the jet stream essentially stops the plume from rising higher into the atmosphere," he says. "Because the jet stream causes the density of the plume to drop so fast, the plume's ability to rise above the jet stream is halted: the jet stream caps the plume at a certain atmospheric level."

Bursik says that new techniques now in development will be capable of producing better estimates of where and when ash clouds from volcanoes will travel.

He and his colleagues have proposed a project with researchers at the University of Alaska that would improve tracking estimates to find out where volcanic ash clouds are going.

"What we get now is a mean estimate of where ash should be in atmosphere," says Bursik, "but our proposal is designed to develop both the mean estimate and estimates of error that would be more accurate and useful. It could help develop scenarios that would provide a quantitative probability as to how likely a plane is to fly through the plume, depending on the route."

Bursik also is working with other researchers at UB, led by UB geology professor Greg Valentine, on a project called VHub, a 'cyber infrastructure for collaborative volcano research and mitigation.'

VHUB would speed the transfer of new tools developed by volcanologists to the government agencies charged with protecting the public from the hazards of volcanic eruptions. That international project, which Valentine heads up at UB, with researchers at Michigan Technological University and the University of South Florida, was funded recently by the National Science Foundation.